It is desirable to permit, as far as possible, fully automatic handling of samples and reagents in analysis devices, so that no manual handling steps are necessary. This allows for simplification and acceleration of many analysis procedures and, still further, reduction of mistakes due to human error during the analysis procedure.
Stringent demands are placed on automatic analysis devices, especially in large-scale laboratories in which a high sampling rate must be permitted. Here, the analysis devices must be able to deliver the large number of reaction vessels with different samples and must be able to allocate these to different reagent containers. In this respect, pipetting devices, inter alia, are used to permit analysis of a sample, by addition of the corresponding reagents, and also further sampling processing steps. Thus, with fully automatic treatment of reagents and samples, even labor-intensive analysis procedures can be performed reliably and quickly, without requiring the involvement of specialized personnel for specialized analysis procedures. A demand placed on a fully or partially automated analysis procedure is, for example, the handling of sample quantities of different sizes, which require a corresponding quantity of reagents. A fully automatic analysis system has to satisfy a wide variety of requirements. There are analysis systems with a high throughput and others with a low throughput, as outlined in brief below.
In analysis systems for low throughput of reagents, the cycle time for liquid removal is approximately 4 to 10 seconds, with the pipetting needle piercing the vessel lid upon each removal. The reagent cartridge has a relatively long dwell time on the device, because of the low throughput. The dwell time is extended still further if the reagent cartridge contains seldom used reagents which are not often called upon and the reagent cartridge contains seldom used reagents which are not often called upon and which accordingly can remain for up to 4 weeks in the analysis system with low throughputs. In these reagent cartridges, there is a need for a high level of protection against evaporation.
In analysis systems distinguished by a high throughput of reagents, there is generally a short cycle time of between 1 and 4 seconds for the pipetting and the positioning of reagent rotor and pipetting needle. Because of the short cycle time, piercing of the funnels with the pipetting needle is not possible. Because of the high throughput of the reagents, the dwell time of the respective reagent cartridges on such analysis systems is only one to two days, for which reason an evaporation from an open flask can be tolerated here.
The handling of very small volumes is described for example in EP 0 564 970. The document discloses reagent containers which permit the removal of small volumes, and in which an evaporation or ageing of the remaining fluid in the container during further processing steps is avoided.
For this purpose, the reagent container has a suitably designed lid which, on the one hand, is suitable for removal of liquid, and, on the other hand, suppresses evaporation of the contents of the container. The lid has, in the middle of its base, a circular opening which is directed into the lid interior and opens out in a conical tip. For removing a sample, the tip of the cone is first pierced, so that a pipetting needle which is provided for removing very small sample quantities, can then be introduced into the vessel.
When the reagent has been removed from the vessel, a small opening remains exclusively at the tip of the cylinder. After removal of the sample, the small opening at the cylinder tip of the tip also ensures that almost no liquid evaporates from the reagent container and that the content of the vessel does not undergo changes due to the contact with, for example, atmospheric humidity or oxygen in the environment. Further details of this vessel closure can be taken from the prior art.
However, if a higher throughput and shorter processing time is necessary, the pipetting device, if it is to permit efficient handling of samples, may be equipped with correspondingly large pipetting tips to take up liquid. To ensure that in this case, too, the larger pipetting tips can still be inserted into the interior of the reagent vessel, a larger opening in the lid will be necessary.
As is described in U.S. Pat. No. 6,255,101 and U.S. Pat. No. 3,991,896, openings in a closure of a reagent vessel can be performed by means of a ball being pressed through the shaft of the reagent vessel lid with the aid of a pin. The ball is pushed into the interior of the reagent container, so that reagent liquid can then be removed through the shaft. Other possibilities, for example piercing a closure cap by means of a cannula as in document WO 83/01912, are conceivable as well. The diameter of the opening can be chosen according to the size of the shaft or the cannula.
In the prior art, this type of sample handling is used for example in analysis systems in the field of clinical-chemical analysis of biological samples. To remove a desired quantity of liquid reagent, the reagent is removed from the open reagent container and is transferred by means of an automatic pipetting device into a reaction cuvette. For each pipetting procedure, an electromechanically driven arm of the pipetting device is guided to an open reagent container, so that handling of samples can take place in the desired manner. The content of a standard reagent container in this case is sufficient for a large number of pipetting procedures. In this connection, it has been found that fluid evaporates during the analysis method before it can be completely used up, on the one hand through the removal of the reagent closure, and on the other hand through the creation of a large opening in a closure cap. Especially in rooms with low atmospheric humidity, considerable amounts of the reagent solution are often lost through evaporation. One consequence thereof is that the evaporation causes an increase in the concentration of the reagent in the fluid. By contrast, the volume of the reagent solution increases when using open reagent containers in rooms with relatively high atmospheric humidity, or through condensation water forming when cooled reagents are used, so that the reagent concentration decreases over the course of time. Moreover, when open reagent containers are used, there is an exchange of gas with the surrounding air, which among other things causes ageing of a reagent. Such effects on the reagent, in particular in the reagent concentration, result in a deterioration in the analysis precision. It has additionally been found that a removal of the reagent closure often has to be done manually. Under these circumstances, the laboratory personnel must take new reagent containers from their packaging and first of all remove the closure in order then to place the open reagent container in the analysis system in place of an empty reagent container. Since it often happens that many different reagents are needed at different times in one and the same analysis system, a manual handling by laboratory personnel requires considerable labor and time. When reclosing the containers, it must be additionally be ensured that the closures are not mixed up. In procedures carried out manually, the possible confusion of the closures represents a source of uncertainty.
In the prior art, therefore, methods are described which permit automatic removal of a reagent container closure. Document EP 0 930 504 discloses a lid-gripping device which is intended for automatic handling of a lid on sample vessels. The lid of the sample vessels in this case has a spike around which the lid-gripping device can grip. By means of a chuck, the lid is held so securely that, when the lid-gripping device is lifted, the lid is completely detached from the vessel, while a holding-down sleeve holds the vessel down to prevent lifting of the vessel.
The document U.S. Pat. No. 5,846,489 likewise discloses an automatic system for opening reagent vessels. According to this solution, a pin of a gripping device is inserted into a groove provided for this purpose in the lid. At one end, the pin has a bead which allows the pin to be clamped in the groove of the lid. The lid can then be removed from the reagent vessel by lifting the pin.
Moreover, U.S. Pat. No. 5,064,059 is related to a device which allows a lid to be removed from the reagent vessel. However, the prior art described herein discloses only an automatic opening of reagent vessels closed by a stopper. Usually, stoppers are only used to close test tubes in which, for example, blood or another liquid from the human or animal body is received, but not reagent vessels. A disadvantage of the prior art is in this case that the mechanisms described do not permit opening of a screw-type closure of a reagent vessel. In practice, however, it has been found that for reagent vessels which often contain a volatile fluid, a screwable closure is particularly suitable, since such a screw-type closure guarantees a reliable sealing of the vessel.
In the prior art, U.S. Pat. No. 6,216,340 describes the removal of a reagent closure which is secured on the vessel by screwing. In this case, opener and reagent lid interact in the manner of a bayonet closure. Through a guide groove formed in the reagent closure, the automatic opener can insert a pin along the guide groove by rotation into the lid, until this is mounted against a limit stop of the guide groove. If the rotational movement is continued in this direction, turning the lid off from the reagent vessel is possible. By rotating the opener in the opposite direction, the connection between lid and opener is released again. A disadvantage of the prior art is the fact that a precise production of the bayonet closure on the lid is an essential requirement for ensuring the functional reliability of the system. The screwing operation, after filling of the vessel, must guarantee a narrowly tolerated angle position of the bayonet closure and also have a good sealing effect.
Moreover, the opener must be guided with precision to the respective reagent vessel to permit engagement of the pin of the opener in the bayonet closure. This requires either a precise placement of the reagent vessels in the analysis system or a detection of position by the analysis system for the respective reagent vessel. Moreover, complex tools are needed for producing the reagent lid, with the result that the production costs are increased. Particularly in the case of reagent vessels handled as disposable articles, this is a considerable disadvantage. Before the opener, after removal of a first lid, can be used again to open reagent vessels, the lid additionally has to be removed from the opener. In the example described, additional measures are needed to do this, which measures permit rotation of the lid in the opposite direction, so that the lid can be removed from the opener.
EP 1 452 869 A2 is related to a system for automatic opening of reagent vessels. The reagent cartridge opening module for opening reagent vessels comprises a carrier which, at its lower end, has a catch element. The catch element locks securely a reagent vessel lid against rotation. Further, a centering unit is guided essentially inside the carrier. The centering unit has at its lower end a snap-in element which can engage in a snap-fit connection with a reagent vessel lid provided for this purpose, so that the reagent vessel lid clings to the snap-in element and at least partially follows the movement of the snap-in element.
EP 0 383 564 A2, is related to a stopper remover apparatus. A stopper remover is used for automatically removing a stopper in a container. The remover comprises container gripping means for gripping the container in stopper gripping means for gripping the stopper. The stopper gripping means is rotated about an axis by a motor while it grips the stopper. The remover features an annular ring having a plurality of spikes, terminating in points extending from its inner surface, the spikes being generally disposed on the ring so as to be non-radially aligned. The result is that the spikes positively grip the stopper only when rotated in the one direction, and slip off the stopper when rotated in an opposite direction.
U.S. Pat. No. 3,830,390 is related to a safety closure for medicine bottles or the like. That safety closure for a container has a threaded neck. The closure consists of a relatively stiff, inner-threaded cap and a relatively resilient outer driver. The inner cap has a circular top and a cylindrical skirt. There are a plurality of ribs on the outer side of the cap skirt at the periphery of the top. The driver has a cylindrical skirt and a top and is telescopically fitted over the cap. There is a series of inwardly and downwardly extending lugs at the inner side of the junction of the top and skirt of the driver. A spacer at the center top of the cap holds the driver in normal, vertically spaced position. The lugs have vertical front edges which extend downwardly a distance sufficient to extend between and engage the ribs for driving the cap onto the container neck. The lugs also have vertical back edges which do not extend downwardly such distance when the driver is in normal position. The cap is removed from the container by flexing the periphery of the driver downwardly to engage the back edges of the lugs with the grips on the cap. In another embodiment, the spacer is annular and holds the rim of the driver up, the lugs and ribs are at inner annular areas, the overcap and driver, respectively, and the central portion of the top of the overcap is flexed downwardly to engage the back edges of the lugs with the grips for unscrewing the cap.
U.S. Pat. No. 5,862,934 is related to a packaging system for liquid reagents. According to this packaging system for liquid reagents, two or more vessels with holding areas are combined by pressing a plug-on plate onto the holding areas of the vessels. For this purpose, the plug-on plate has two or more apertures, the cross-section of which essentially corresponds to the cross-section of the holding areas of the vessels. Plug-on plate and/or holding areas of the vessels can have stop elements, which, after the combination, hinder the separation vessels and plug-on plate.
The prior art solution according to EP 1 452 869 A2 is related to decapping of reagent containers with snap-on ball fixing. According to this system, a cartridge system includes at least one container having a threadedly fixed lid, to be opened and unthreaded and subsequently to be trashed. The system according to EP 1 452 869 A2 is limited insofar as, according to this solution, only one threaded lid is engaged by the system at a time. This limits the performance and does not allow for parallel processing. Further, only one height of a cartridge system and only one standardized height of containers to be opened is processed. This likewise limits the performance of the system according to EP 1 452 869 A2. A centering pin by means of which a lid is being seized after being unscrewed is essentially unprotected and therefore prone to damage. The screwing head requires for normal function exact positioning and does not compensate for more tolerances, such as tolerances which are inherent to manufacturing of the cartridge systems. Still further, the solution according to EP 1 452 869 A2 does not provide from active gripping positioning and holding of the cartridge during the unscrewing, i.e. the opening process of a single container provided with a threaded lid. Still further, for getting rid of the lid unscrewed and for performing a vertical movement of the screwing head, an additional horizontal movement or a rotational movement of the screwing head above a trash-opening is required.